Massive endocytosis mechanisms are involved in uptake of HIV-1 particles by monocyte-derived dendritic cells

Authors:

Fernando Laguía, Jakub Chojnacki, Itziar Erkizia, María Isabel Geli, Carlos Enrich, Javier Martinez-Picado, Patricia Resa-Infante

Keywords:

dendritic cells; CD169/Siglec1; HIV; sac-like compartment; MEND

Abstract:

Introduction: HIV-1 exploits dendritic cells (DCs) to spread throughout the body via specific recognition of gangliosides present on the viral envelope by the CD169/Siglec-1 membrane receptor. This interaction triggers the internalization of HIV-1 within a structure known as the sac-like compartment. While the mechanism underlying sac-like compartment formation remains elusive, prior research indicates that the process is clathrin-independent and cell membrane cholesterol–dependent and involves transient disruption of cortical actin. Here, we investigate the potential involvement of massive endocytosis (MEND) in this process.

Methods: We used live cell confocal imaging to measure the dimensions and dynamics of the compartment. We assessed the role of actin and cholesterol in fixed and live cells using confocal microscopy and evaluated the effect of PI3K and protein palmytoilation inhibitors during viral uptake.

Results: Our data demonstrate extensive plasma membrane invagination based on sac-like compartment dimensions (2.9 μm in diameter and 20 μm³ in volume). We showed that the cholesterol concentration doubles within the regions of viral uptake, suggesting lipid-phase separation, and that development of the sac-like compartment is accompanied by transient depolarization of cortical actin. Moreover, we observed that protein palmitoylation and PI3K inhibition reduce the sac-like compartment formation rate from 70% to 20% and 40%, respectively.

Conclusions: Our results indicate the involvement of MEND mechanisms during sac-like compartment formation.

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